Disease relevance of MK 771

• TRH, DN-1417, MK-771 and TSII-37 were injected 10 min before the head injury [1].
• Methysergide acts synergistically with MK-771 to combat the sudden fall in pressure induced by acute hemorrhage in the anesthetised cat [2].
• Propranolol, at a dose of 7 nmol, and methylatropine at a dose of 0.5 nmol, significantly inhibited the tachycardia produced by MK-771 [3].
• TRH and MK 771 were shown to act within the brain to reverse endotoxic shock hypotension; at the doses used, the pressor effects of these two tripeptides were achieved through selectively different actions upon heart rate and pulse pressure [4].
• 3. 5-HTP potentiated MK-771-induced hyperthermia [5].

Psychiatry related information on MK 771

• MK-771 and other TRH analogs may represent novel agents for improving memory deficits produced by cholinergic insufficiency in Alzheimer's disease [6].
• After the swimming test, locomotor activity remarkably decreased in the control rats, while decreased locomotor activity was partially prevented in the TRH, DN-1417, MK-771 and amitriptyline treated rats which exhibited active movement not only during the swimming period but also after it [7].
• Preliminary studies on the effects of a TRH analog, MK-771, in an animal model of Alzheimer's disease [8].

High impact information on MK 771

• Thyrotropin-releasing hormone and its analog MK-771 increase the cerebroventricular perfusate content of dihydroxyphenylacetic acid [9].
• MK-771 [L-N-(2-oxopiperidin-6-YL-carbonyl)-L-histidyl-L-thiazolidine-4-carboxamide], a TRH analog with enhanced central nervous system effects, had effects on AVP and OT release comparable to equimolar doses of TRH [10].
• 1-NP (4 mumol/kg) also antagonized twitching following the direct 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (6 mumol/kg i.p.) but not after the thyrotropin releasing hormone analog MK-771 (20 mumol/kg i.p.) in rats [11].
• However, blood flow was elevated by MK-771 in spinal cord and brain [12].
• MK-771 (0.01-5.0 micrograms i.t.) caused dose-related increases in mean arterial pressure (MAP) and heart rate (HR) [12].

Biological context of MK 771

• MK-771 had no effect on vascular resistance locally or in other central nervous system structures [12].
• Treatment of rats with the TRH analog MK-771. Down-regulation of TRH receptors and behavioral tolerance [13].
• MK-771, at a dose of 125 pmol (50 ng), produced significant increases in both heart rate and blood pressure [3].
• Neither TRH nor MK-771 prevented the [D-Arg]-SP-induced vasoconstriction [14].
• Metabolism of the TRH analog L-pyro-2-aminoadipyl-L-histidyl-[3H]-L-thiazolidine-4-carboxamide (MK-771) in gut and brain tissue of rats: the implications for its bioavailability [15].

Anatomical context of MK 771

• Bilateral injection of TRH (5.0 micrograms total dose) and the analogues RX 77368 (0.01-1.0 microgram), CG 3509 (0.1-1.0 microgram), DN-1417 (1.0 microgram) and MK-771 (1.0 microgram) into the nucleus accumbens reduced the pentobarbitone-induced sleeping time [16].
• Assessment of changes in regional blood flow and vascular resistance with the radioactive microsphere technique showed that MK-771 increased total peripheral resistance and vasoconstricted cutaneous, skeletal muscle, adrenal, renal and intestinal vascular beds [12].
• Administration of MK-771, a stable TRH analog, to such animals restored HACU activity in hippocampus to normal levels [6].
• The present study investigated the mechanism by which the TRH analog MK-771 produces these effects when injected into the preoptic suprachiasmatic nucleus (POSC) [3].
• Degradation of unabsorbed MK-771 occurred mainly in the large intestine of normal rats presumably because of the action of gut flora [15].

Associations of MK 771 with other chemical compounds

• Effects of behaviorally active doses of thyrotropin-releasing hormone and its analog MK-771 on dopaminergic neuronal systems in the brain of the rat [17].
• The MAP response to MK-771 was blocked by peripheral administration of pentolinium or phentolamine, and was partially attenuated by adrenalectomy [12].
• The effects of thyrotropin-releasing hormone (TRH) and an analog of this hormone, MK-771, were determined on body shaking behavior and on biochemical estimates of the activity of dopamine (DA) neurons in the rat [17].
• Intravenous injection of the synthetic TRH analog, MK-771, to anesthetised cats raised the blood pressure by a central mechanism, i.e. by activating the outflow of sympathetic stimuli from the CNS to the periphery and raising the plasma concentration of adrenaline and noradrenaline [2].
• The TRH analogue MK-771, increases acetylcholine release in hippocampus but not striatum of the conscious rat [18].

Gene context of MK 771

• Intracisternally administered neurotensin, which did not affect EMG activity by itself, antagonized the actions of MK-771 while somatostatin was inactive in this regard [19].
• Behaviorally active doses of TRH (20 mg/kg, i.p.), MK-771 (2 mg/kg, i.p.) and DN-1417 (10 mg/kg, i.p.) also failed to elevate serum prolactin levels in both ovariectomized rats and normal male rats [20].
• Furthermore, following daily administration of MK-771 (0.5 mg/kg, s.c.) for 20 days, serum prolactin levels remained unchanged in male rats [20].
• 6. Ipsapirone, a 5-HT1A-active drug purported both as an agonist and as an antagonist, inhibited MK-771-evoked WDS, like 8-OH-DPAT, but did not induce the serotonin syndrome, unlike 8-OH-DPAT [5].
• TRH was more potent than MK-771 in altering punished response rates maintained by either event [21].

Analytical, diagnostic and therapeutic context of MK 771

• The effect of the two analogs of thyrotropin-releasing hormone (TRH), namely MK-771 and DN-1417, administered peripherally, on the actions of morphine and loperamide on gastrointestinal transit, was investigated in mice [22].
• Interestingly, although RX77368 and MK-771 appear to have similar TRH receptor affinities to CG3703, the former analogs have shown less beneficial effects in animal models of spinal injury.(ABSTRACT TRUNCATED AT 250 WORDS)[23]
• Propranolol and methylatropine antagonize the cardiovascular effects produced by microinjection of the TRH analog MK-771 into the preoptic suprachiasmatic nucleus [3].
• Intraperitoneal injections of TRH (20, 40 mg/kg), MK-771 (0.5-4 mg/kg) or DN-1417 (5-20 mg/kg) elicited marked body shaking in male rats [20].

References